In eukaryotic organisms, changes in cell phenotype are tightly associated with dynamic changes in the epigenome. Over the past few years, sequencing-based genome-wide approaches to generate, analyze, interpret and integrate epigenetic information have been applied to investigate the mechanisms behind the changes in cell status, such as those which are seen in differentiation, disease and reprogramming. This article focuses on the four types of epigenomic information (i.e., nucleosome positioning, histone modification, DNA methylation and chromatin higher-order structure). We summarize the distinct high-throughput sequencing applications used to generate the different types of epigenomic profiles and the bioinformatic software available for performing routine analysis. With the dramatic improvement of sequencing technology and bioinformatic analysis, epigenome sequencing has gradually become the common approach to study a variety of biological issues.